1.Supramolecular prodrug inspiried by the Rhizoma Coptidis - Fructus Mume herbal pair alleviated inflammatory diseases by inhibiting pyroptosis.
Wenhui QIAN ; Bei ZHANG ; Ming GAO ; Yuting WANG ; Jiachen SHEN ; Dongbing LIANG ; Chao WANG ; Wei WEI ; Xing PAN ; Qiuying YAN ; Dongdong SUN ; Dong ZHU ; Haibo CHENG
Journal of Pharmaceutical Analysis 2025;15(2):101056-101056
Sustained inflammatory responses are closely related to various severe diseases, and inhibiting the excessive activation of inflammasomes and pyroptosis has significant implications for clinical treatment. Natural products have garnered considerable concern for the treatment of inflammation. Huanglian-Wumei decoction (HLWMD) is a classic prescription used for treating inflammatory diseases, but the necessity of their combination and the exact underlying anti-inflammatory mechanism have not yet been elucidated. Inspired by the supramolecular self-assembly strategy and natural drug compatibility theory, we successfully obtained berberine (BBR)-chlorogenic acid (CGA) supramolecular (BCS), which is an herbal pair from HLWMD. Using a series of characterization methods, we confirmed the self-assembly mechanism of BCS. BBR and CGA were self-assembled and stacked into amphiphilic spherical supramolecules in a 2:1 molar ratio, driven by electrostatic interactions, hydrophobic interactions, and π-π stacking; the hydrophilic fragments of CGA were outside, and the hydrophobic fragments of BBR were inside. This stacking pattern significantly improved the anti-inflammatory performance of BCS compared with that of single free molecules. Compared with free molecules, BCS significantly attenuated the release of multiple inflammatory mediators and lipopolysaccharide (LPS)-induced pyroptosis. Its anti-inflammatory mechanism is closely related to the inhibition of intracellular nuclear factor-kappaB (NF-κB) p65 phosphorylation and the noncanonical pyroptosis signalling pathway mediated by caspase-11.
2.RAD51B-AS1 promotes the malignant biological behavior of ovarian cancer through upregulation of RAD51B
WEI XINYI ; WANG CONGHUI ; TANG SANGSANG ; YANG QIAN ; SHEN ZHANGJIN ; ZHU JIAWEI ; CHENG XIAODONG ; WANG XINYU ; XIE XING ; XU JUNFEN ; LU WEIGUO
Journal of Zhejiang University. Science. B 2024;25(7):581-593,中插4-中插16
Long non-coding RNAs(lncRNAs)play an indispensable role in the occurrence and development of ovarian cancer(OC).However,the potential involvement of lncRNAs in the progression of OC is largely unknown.To investigate the detailed roles and mechanisms of RAD51 homolog B-antisense 1(RAD51B-AS1),a novel lncRNA in OC,reverse transcription-quantitative polymerase chain reaction(RT-qPCR)was performed to verify the expression of RAD51B-AS1.Cellular proliferation,metastasis,and apoptosis were detected using the cell counting kit-8(CCK-8),colony-formation,transwell,and flow cytometry assays.Mouse xenograft models were established for the detection of tumorigenesis.The results revealed that RAD51B-AS1 was significantly upregulated in a highly metastatic human OC cell line and OC tissues.RAD51B-AS1 significantly increased the proliferation and metastasis of OC cells and enhanced their resistance to anoikis.Biogenetics prediction analysis revealed that the only target gene of RAD51B-AS1 was RAD51B.Subsequent gene function experiments revealed that RAD51B exerts the same biological effects as RAD51B-AS1.Rescue experiments demonstrated that the malignant biological behaviors promoted by RAD51B-AS1 overexpression were partially or completely reversed by RAD51B silencing in vitro and in vivo.Thus,RAD51B-AS1 promotes the malignant biological behaviors of OC and activates the protein kinase B(Akt)/B cell lymphoma protein-2(Bcl-2)signaling pathway,and these effects may be associated with the positive regulation of RAD51B expression.RAD51B-AS1 is expected to serve as a novel molecular biomarker for the diagnosis and prediction of poor prognosis in OC,and as a potential therapeutic target for disease management.
3.Establishment and evaluation of a neutralizing antibody detection model for West Nile virus pseudovirus
Wanlu ZHU ; Nan CHEN ; Xiangjun HAO ; Junjuan FENG ; Xing LU ; Jing WANG ; Guojiang CHEN ; Chunxia QIAO ; Xinying LI ; Chenghua LIU ; Beifen SHEN ; Jiannan FENG ; Jun ZHANG ; He XIAO
Chinese Journal of Experimental and Clinical Virology 2024;38(2):188-192
Objective:To establish an in vivo infection model of West Nile virus (WNV) pseudovirus and evaluate the neutralizing activity of antibody WNV-XH1.Methods:A stable cell line that can package the WNV pseudovirus was established in the early stage to prepare the pseudovirus supernatant. The supernatant was concentrated and infected BHK21 cells to detect the titer of the pseudovirus. After intraperitoneal injection of the pseudovirus into C57BL/J mice, bioluminescence imaging was performed to observe the infection status of the pseudovirus in the mice. After simultaneous infection, blood was collected and ELISA was used to detect NS1 levels in mouse serum. The in vivo functional activity of antibody WNV-XH1 was evaluated using the established mouse infection model.Results:Fluorescence was detected in C57BL/J mice infected with WNV pseudovirus, and the NS1 levels in the peripheral blood serum of mice infected with pseudovirus were significantly higher than those of non infected mice (1.453±0.09vs0.305±0.018). After intravenous administration of WNV-XH1 antibody before the attack, the fluorescence signal in the mice decreased and the serum NS1 level decreased (0.384±0.015).Conclusions:A successful in vivo infection model of WNV pseudovirus was established, and it was confirmed that the antibody WNV-XH1 had a protective effect against WNV pseudovirus infection in vivo.
4.Experts consensus on standard items of the cohort construction and quality control of temporomandibular joint diseases (2024)
Min HU ; Chi YANG ; Huawei LIU ; Haixia LU ; Chen YAO ; Qiufei XIE ; Yongjin CHEN ; Kaiyuan FU ; Bing FANG ; Songsong ZHU ; Qing ZHOU ; Zhiye CHEN ; Yaomin ZHU ; Qingbin ZHANG ; Ying YAN ; Xing LONG ; Zhiyong LI ; Yehua GAN ; Shibin YU ; Yuxing BAI ; Yi ZHANG ; Yanyi WANG ; Jie LEI ; Yong CHENG ; Changkui LIU ; Ye CAO ; Dongmei HE ; Ning WEN ; Shanyong ZHANG ; Minjie CHEN ; Guoliang JIAO ; Xinhua LIU ; Hua JIANG ; Yang HE ; Pei SHEN ; Haitao HUANG ; Yongfeng LI ; Jisi ZHENG ; Jing GUO ; Lisheng ZHAO ; Laiqing XU
Chinese Journal of Stomatology 2024;59(10):977-987
Temporomandibular joint (TMJ) diseases are common clinical conditions. The number of patients with TMJ diseases is large, and the etiology, epidemiology, disease spectrum, and treatment of the disease remain controversial and unknown. To understand and master the current situation of the occurrence, development and prevention of TMJ diseases, as well as to identify the patterns in etiology, incidence, drug sensitivity, and prognosis is crucial for alleviating patients′suffering.This will facilitate in-depth medical research, effective disease prevention measures, and the formulation of corresponding health policies. Cohort construction and research has an irreplaceable role in precise disease prevention and significant improvement in diagnosis and treatment levels. Large-scale cohort studies are needed to explore the relationship between potential risk factors and outcomes of TMJ diseases, and to observe disease prognoses through long-term follw-ups. The consensus aims to establish a standard conceptual frame work for a cohort study on patients with TMJ disease while providing ideas for cohort data standards to this condition. TMJ disease cohort data consists of both common data standards applicable to all specific disease cohorts as well as disease-specific data standards. Common data were available for each specific disease cohort. By integrating different cohort research resources, standard problems or study variables can be unified. Long-term follow-up can be performed using consistent definitions and criteria across different projects for better core data collection. It is hoped that this consensus will be facilitate the development cohort studies of TMJ diseases.
5.Effectiveness of LEARNS model combined with video health education in patients undergoing painless gastrointestinal endoscopy
Yafang ZHU ; Xing ZHANG ; Xuefang XIE ; Nannan SHEN
Chinese Journal of Modern Nursing 2024;30(26):3626-3630
Objective:To explore the effectiveness of LEARNS model combined with video health education in patients undergoing painless gastrointestinal endoscopy.Methods:From February 2021 to November 2022, convenience sampling was used to select 128 patients who underwent painless gastrointestinal endoscopy at the Endoscopy Center of Affiliated Hospital of Shaoxing University as research subjects. A total of 64 patients admitted from February to December 2021 served as control group, while 64 patients admitted from January to November 2022 served as observation group. Control group patients received routine health education, while observation group was treated with LEARNS model combined with video health education on the basis of control group. The degree of cooperation, psychological state, and satisfaction with health education were compared between two groups of patients.Results:The proportion of patients in observation group who actively cooperated was higher than that in control group, and there was a statistically significant difference in the degree of cooperation between the two groups ( P<0.05). Thirty minutes before and after the endoscopy, the scores of both subscales of the State-Trait Anxiety Inventory (STAI) in observation group were lower than those in the control group, and the difference was statistically significant ( P<0.05). The satisfaction scores of observation group patients with health education in all dimensions were higher than those of control group, and the differences were statistically significant ( P<0.05) . Conclusions:LEARNS model combined with video health education can effectively improve the cooperation of patients undergoing painless gastrointestinal endoscopy, alleviate their pre-examination anxiety, and enhance their satisfaction with health education, which is worthy of clinical practice.
6.Melatonin Ameliorates Abnormal Sleep-Wake Behavior via Facilitating Lipid Metabolism in a Zebrafish Model of Parkinson's Disease.
Meng-Zhu PANG ; Han-Xing LI ; Xue-Qin DAI ; Xiao-Bo WANG ; Jun-Yi LIU ; Yun SHEN ; Xing XU ; Zhao-Min ZHONG ; Han WANG ; Chun-Feng LIU ; Fen WANG
Neuroscience Bulletin 2024;40(12):1901-1914
Sleep-wake disorder is one of the most common nonmotor symptoms of Parkinson's disease (PD). Melatonin has the potential to improve sleep-wake disorder, but its mechanism of action is still unclear. Our data showed that melatonin only improved the motor and sleep-wake behavior of a zebrafish PD model when melatonin receptor 1 was present. Thus, we explored the underlying mechanisms by applying a rotenone model. After the PD zebrafish model was induced by 10 nmol/L rotenone, the motor and sleep-wake behavior were assessed. In situ hybridization and real-time quantitative PCR were used to detect the expression of melatonin receptors and lipid-metabolism-related genes. In the PD model, we found abnormal lipid metabolism, which was reversed by melatonin. This may be one of the main pathways for improving PD sleep-wake disorder.
Animals
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Zebrafish
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Melatonin/pharmacology*
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Lipid Metabolism/drug effects*
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Disease Models, Animal
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Rotenone/pharmacology*
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Sleep Wake Disorders/metabolism*
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Parkinson Disease/metabolism*
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Motor Activity/drug effects*
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Sleep/drug effects*
7.Effect of Bufeitang on Lung-gut Axis in Rats with Lung Qi-deficiency Syndrome of Chronic Obstructive Pulmonary Disease
Junxi SHEN ; Xing ZHU ; Yunzhi CHEN ; Huaiquan LIU ; Cancan CHU ; Yu ZHANG ; Gang SU ; Wen LI ; Changjun XU ; Pingzhen TONG ; Xinran YU ; Guangyong YANG ; Ying DENG
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(7):47-56
ObjectiveTo investigate the effect of Bufeitang on intestinal flora of rats with lung Qi-deficiency syndrome of chronic obstructive pulmonary disease(COPD), and to explore the mechanism of traditional Chinese medicine in regulating intestinal flora and thus restoring the balance of lung-gut axis. MethodA total of 84 rats were randomly divided into 7 groups, including blank group, model group, fecal bacterial transplantation(FMT) group, dexamethasone group and low, medium and high dose groups of Bufeitang, 12 rats in each group. Except for the blank group, cigarette and sawdust fumigation combined with intratracheal instillation of lipopolysaccharide(LPS) were used to establish the COPD rat model with lung Qi-deficiency syndrome in all other groups. The low, medium and high dose groups of Bufeitang were intragastric administrated with Bufeitang(3.645, 7.29, 14.58 g·kg-1), the FMT group was given fecal bacteria liquid enema(10 mL·kg-1), dexamethasone group was given dexamethasone acetate tablet suspension by gavage(0.135 mg·kg-1), the blank group and model group were given equal amount of distilled water. Fresh feces were collected after 28 d of continuous intervention for 16S rRNA gene sequencing. Lung and colon tissues were stained with hematoxylin-eosin(HE) for pathomorphological observation, and enzyme-linked immunosorbent assay (ELISA) was performed to detect the contents of tumor necrosis factor-α(TNF-α) and interleukin-8(IL-8) in lung tissues. ResultCompared with the blank group, the model group showed severe abnormal lung tissue structure with alveolar atrophy and collapse accompanied by severe inflammatory cell infiltration. Compared with the model group, the extent of injury was significantly improved, and inflammatory cell infiltration was reduced with basically normal alveolar structure in the high dose group of Bufeitang. Compared with the blank group, the model group had severely abnormal colonic tissue structure, the epithelial cells in the mucosal layer were eroded and shed, the number of inflammatory cells increased, the submucosal layer was edematous and the gap was enlarged. Compared with the model group, the extent of damage was significantly improved in the medium and high dose groups of Bufeitang, the epithelial cells in the mucosal layer were neatly and closely arranged, with only a small amount of inflammatory cell infiltration and no significant degeneration. Compared with the blank group, the TNF-α and IL-8 levels of lung tissue in the model group were significantly increased(P<0.01). Compared with the model group, the TNF-α and IL-8 levels of lung tissues in the low, medium and high dose groups of Bufeitang were significantly decreased(P<0.01). Bufeitang significantly modulated the number of bacteria species as well as alpha and beta diversity of model rats, corrected the return of intestinal flora to normal abundance and diversity, and positively regulated 4 differential phyla(such as Firmicutes, Proteobacteria) and 13 differential genera(such as Turicibacter, Lactobacillus, Anaerobiospirillum, Intestinimonas) in COPD model rats with lung Qi-deficiency syndrome, and down-regulated 2 carbohydrate metabolic pathway functions, including the pentose phosphate pathway(non-oxidative branch) Ⅰ and the Calvin-Benson-Bassham cycle. ConclusionBufeitang can modulate the abundance and diversity of intestinal flora species, affect the function of metabolic pathways, repair the structure of lung and colon tissues, regulate the level of inflammatory factors, and thus improve COPD with lung Qi-deficiency syndrome. The mechanism may be related to its regulation of inflammation-related intestinal flora to restore the balance of lung-gut axis in COPD with lung Qi-deficiency syndrome.
8.The effect and mechanism of metformin on peripheral neuropathy in type 1 diabetic rats
Xing WANG ; Cai-na LI ; Lin ZHANG ; Wen-ming JI ; Lei LEI ; Hui CAO ; Quan LIU ; Yi HUAN ; Su-juan SUN ; Shuai-nan LIU ; Zhu-fang SHEN
Acta Pharmaceutica Sinica 2023;58(2):386-395
Diabetic peripheral neuropathy (DPN) is one of the most common microvascular complications occurring in both type 1 and type 2 diabetes mellitus patients, which often results in patients suffering from severe hyperalgesia and allodynia. Up to now, the clinical therapeutic effect of DPN is still unsatisfactory. Metformin is an anti-diabetic drug that has been safely and widely used for the treatment of type 2 diabetes for decades. Studies have shown that metformin can improve pain caused by DPN, but its effects on the nerve conduction velocity and morphology of the sciatic nerve of DPN, and the mechanism for improving DPN are not clear. Therefore, the STZ-induced model of type 1 DPN in SD rats was used to study the effects of metformin on DPN, and to preliminarily explore its mechanism in this study. All animal experiments were carried out with approval of the Experimental Animal Welfare Ethics Committee of the Institute of Materia Medica (Chinese Academy of Medical Sciences and Peking Union Medical College). After the model was established successfully, STZ diabetic rats were randomly divided into a model group and a metformin treatment group, and 10 normal SD rats were selected as the normal control group, and the rats were intragastrically administered for 12 weeks. The results showed that metformin significantly reduced blood glucose, glycosylated hemoglobin, food consumption and water consumption in STZ rats. Metformin markedly increased the motor nerve conduction velocity and mechanical stabbing pain threshold, prolonged the hot plate latency threshold, and improved the pathological morphological abnormalities of the sciatic nerve in STZ rats. In addition, metformin increased the content of glutathione (GSH), enhanced the activities of antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT), and reduced the content of malondialdehyde (MDA) in serum and sciatic nerve of STZ diabetic rats, as well as regulating the expression of genes related to oxidative stress in the sciatic nerve. Metformin obviously reduced the levels of pro-inflammatory factors such as tumor necrosis factor
9.Expert consensus for the clinical application of autologous bone marrow enrichment technique for bone repair (version 2023)
Junchao XING ; Long BI ; Li CHEN ; Shiwu DONG ; Liangbin GAO ; Tianyong HOU ; Zhiyong HOU ; Wei HUANG ; Huiyong JIN ; Yan LI ; Zhonghai LI ; Peng LIU ; Ximing LIU ; Fei LUO ; Feng MA ; Jie SHEN ; Jinlin SONG ; Peifu TANG ; Xinbao WU ; Baoshan XU ; Jianzhong XU ; Yongqing XU ; Bin YAN ; Peng YANG ; Qing YE ; Guoyong YIN ; Tengbo YU ; Jiancheng ZENG ; Changqing ZHANG ; Yingze ZHANG ; Zehua ZHANG ; Feng ZHAO ; Yue ZHOU ; Yun ZHU ; Jun ZOU
Chinese Journal of Trauma 2023;39(1):10-22
Bone defects caused by different causes such as trauma, severe bone infection and other factors are common in clinic and difficult to treat. Usually, bone substitutes are required for repair. Current bone grafting materials used clinically include autologous bones, allogeneic bones, xenografts, and synthetic materials, etc. Other than autologous bones, the major hurdles of rest bone grafts have various degrees of poor biological activity and lack of active ingredients to provide osteogenic impetus. Bone marrow contains various components such as stem cells and bioactive factors, which are contributive to osteogenesis. In response, the technique of bone marrow enrichment, based on the efficient utilization of components within bone marrow, has been risen, aiming to extract osteogenic cells and factors from bone marrow of patients and incorporate them into 3D scaffolds for fabricating bone grafts with high osteoinductivity. However, the scientific guidance and application specification are lacked with regard to the clinical scope, approach, safety and effectiveness. In this context, under the organization of Chinese Orthopedic Association, the Expert consensus for the clinical application of autologous bone marrow enrichment technique for bone repair ( version 2023) is formulated based on the evidence-based medicine. The consensus covers the topics of the characteristics, range of application, safety and application notes of the technique of autologous bone marrow enrichment and proposes corresponding recommendations, hoping to provide better guidance for clinical practice of the technique.
10.An evidence-based clinical guideline for the treatment of infectious bone defect with induced membrane technique (version 2023)
Jie SHEN ; Lin CHEN ; Shiwu DONG ; Jingshu FU ; Jianzhong GUAN ; Hongbo HE ; Chunli HOU ; Zhiyong HOU ; Gang LI ; Hang LI ; Fengxiang LIU ; Lei LIU ; Feng MA ; Tao NIE ; Chenghe QIN ; Jian SHI ; Hengsheng SHU ; Dong SUN ; Li SUN ; Guanglin WANG ; Xiaohua WANG ; Zhiqiang WANG ; Hongri WU ; Junchao XING ; Jianzhong XU ; Yongqing XU ; Dawei YANG ; Tengbo YU ; Zhi YUAN ; Wenming ZHANG ; Feng ZHAO ; Jiazhuang ZHENG ; Dapeng ZHOU ; Chen ZHU ; Yueliang ZHU ; Zhao XIE ; Xinbao WU ; Changqing ZHANG ; Peifu TANG ; Yingze ZHANG ; Fei LUO
Chinese Journal of Trauma 2023;39(2):107-120
Infectious bone defect is bone defect with infection or as a result of treatment of bone infection. It requires surgical intervention, and the treatment processes are complex and long, which include bone infection control,bone defect repair and even complex soft tissue reconstructions in some cases. Failure to achieve the goals in any step may lead to the failure of the overall treatment. Therefore, infectious bone defect has been a worldwide challenge in the field of orthopedics. Conventionally, sequestrectomy, bone grafting, bone transport, and systemic/local antibiotic treatment are standard therapies. Radical debridement remains one of the cornerstones for the management of bone infection. However, the scale of debridement and the timing and method of bone defect reconstruction remain controversial. With the clinical application of induced membrane technique, effective infection control and rapid bone reconstruction have been achieved in the management of infectious bone defect. The induced membrane technique has attracted more interests and attention, but the lack of understanding the basic principles of infection control and technical details may hamper the clinical outcomes of induced membrane technique and complications can possibly occur. Therefore, the Chinese Orthopedic Association organized domestic orthopedic experts to formulate An evidence-based clinical guideline for the treatment of infectious bone defect with induced membrane technique ( version 2023) according to the evidence-based method and put forward recommendations on infectious bone defect from the aspects of precise diagnosis, preoperative evaluation, operation procedure, postoperative management and rehabilitation, so as to provide useful references for the treatment of infectious bone defect with induced membrane technique.

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